hypochondroplasia

{{Infobox medical condition (new)

| name = Hypochondroplasia

| synonyms =

| image = File:Autosomal dominant - en.svg

| caption = Hypochondroplasia is autosomal dominant in inheritance.

| pronounce =

| field =

| symptoms = Skeletal dysplasia

| complications =

| onset =

| duration =

| types =

| causes = FGFR3 gene mutation

| risks =

| diagnosis = Physical finding, X-ray

| differential =

| prevention =

| treatment = Special education, Laminectomy

| medication =

| prognosis =

| frequency =

| deaths =

}}

Hypochondroplasia (HCH) is a developmental disorder caused by an autosomal dominant genetic defect in the fibroblast growth factor receptor 3 gene (FGFR3) that results in a disproportionately short stature, micromelia{{cite journal|last1=Bober|first1=Michael B.|last2=Bellus|first2=Gary A.|last3=Nikkel|first3=Sarah M.|last4=Tiller|first4=George E.|title=Hypochondroplasia|journal=GeneReviews|date=1 January 1993|pmid=20301650|url=https://www.ncbi.nlm.nih.gov/books/NBK1477/|access-date=18 December 2016}}update 2013 and a head that appears large in comparison with the underdeveloped portions of the body. It is classified as short-limbed dwarfism.{{cite web |url=http://ghr.nlm.nih.gov/condition=hypochondroplasia |title=Hypochondroplasia - Genetics Home Reference |access-date=2009-03-12}}{{cite web|title=Dwarfism: MedlinePlus|url=https://medlineplus.gov/dwarfism.html|website=NIH|access-date=21 December 2016}}

Signs and symptoms

Individuals affected by this disorder appear normal at birth. As the infant grows, however, their arms and legs do not develop properly, and their body becomes thicker and shorter than normal. The following are characteristics consistent with this condition:{{cite web|title=Hypochondroplasia {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|url=https://rarediseases.info.nih.gov/diseases/6724/hypochondroplasia|website=rarediseases.info.nih.gov|access-date=21 December 2016}}

Brachydactyly
Short stature
Micromelia
Skeletal dysplasia
Abnormality of femur

Cause

Hypochondroplasia is inherited as an autosomal dominant trait affecting the FGFR3 gene on chromosome 4p16.3. There is currently no cure for this condition.

Pathophysiology

File:PDB 1m61 EBI.jpg

This disorder results from mutations in the proximal tyrosine kinase domain of the FGFR3 gene. This gene plays an important role in embryonic development, helping to regulate activities such as cell division, migration and differentiation.{{Cite web |title=Entry - *134934 - FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3 - OMIM - (MIRROR) |url=https://mirror.omim.org/entry/134934 |access-date=2023-02-28 |website=mirror.omim.org}}

Hypochondroplasia can be caused by point mutations such as p. Lys650Asn.{{cite web|title=NM_000142.4(FGFR3):c.1950G>C (p.Lys650Asn) AND Hypochondroplasia - ClinVar - NCBI|url=https://www.ncbi.nlm.nih.gov/clinvar/RCV000017756/|website=www.ncbi.nlm.nih.gov|access-date=21 December 2016}} In FGFR3, some 20 different mutations have been associated with hypochondroplasia,{{cite web|last1=Reference|first1=Genetics Home|title=FGFR3 gene|url=https://ghr.nlm.nih.gov/gene/FGFR3#conditions|website=Genetics Home Reference|access-date=21 December 2016}} and it seems to have a role in skeletal dysplasia.{{cite journal |last1=Foldynova-Trantirkova |first1=Silvie |last2=Wilcox |first2=William R. |last3=Krejci |first3=Pavel |title=Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias |journal=Human Mutation |date=21 December 2016 |volume=33 |issue=1 |pages=29–41 |doi=10.1002/humu.21636|pmc=3240715 |issn=1059-7794 |pmid=22045636}}

Diagnosis

The diagnosis of this condition can be done via X-rays (with lack of normal distance L1 to L5),{{cite web|title=OMIM Entry - # 146000 - HYPOCHONDROPLASIA; HCH|url=https://omim.org/entry/146000|website=omim.org|access-date=21 December 2016}} and additionally genetic testing is available to ascertain hypochondroplasia.{{cite web|title=Hypochondroplasia - Conditions - GTR - NCBI|url=https://www.ncbi.nlm.nih.gov/gtr/conditions/C0410529/|website=www.ncbi.nlm.nih.gov|access-date=21 December 2016}} However, the physical characteristics are one of the most important in determining the condition.

Treatment

File:Spinal Stenosis.png]]

Treatment of hypochondroplasia usually takes the form of orthopedic surgery and physical therapy. Genetic counseling is advised for individuals and their families. Specifically in the case of spinal stenosis, one option is laminectomy.

Prognosis

Life expectancy for individuals with hypochondroplasia is normal; height is about {{convert|132|-|147|cm|ftin}}.{{cite web|last1=RESERVED|first1=INSERM US14 -- ALL RIGHTS|title=Orphanet: Hypochondroplasia|url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=429|website=www.orpha.net|access-date=21 December 2016}}